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Ultrasound-targeted stromal cell-derived factor-1-loaded microbubble destruction promotes mesenchymal stem cell homing to kidneys in diabetic nephropathy rats.

Wu S, Li L, Wang G, Shen W, Xu Y, Liu Z, Zhuo Z, Xia H, Gao Y, Tan K - Int J Nanomedicine (2014)

Bottom Line: The related bioeffects were also elucidated.In the in vivo study, SDF-1 was successfully released in the targeted kidneys.In conclusion, ultrasound-targeted MB(SDF-1) destruction could promote the homing of MSCs to early DN kidneys and provide a novel potential therapeutic approach for DN kidney repair.

View Article: PubMed Central - PubMed

Affiliation: Department of Ultrasound, Third Military Medical University, Chongqing, People's Republic of China.

ABSTRACT
Mesenchymal stem cell (MSC) therapy has been considered a promising strategy to cure diabetic nephropathy (DN). However, insufficient MSCs can settle in injured kidneys, which constitute one of the major barriers to the effective implementation of MSC therapy. Stromal cell-derived factor-1 (SDF-1) plays a vital role in MSC migration and involves activation, mobilization, homing, and retention, which are presumably related to the poor homing in DN therapy. Ultrasound-targeted microbubble destruction has become one of the most promising strategies for the targeted delivery of drugs and genes. To improve MSC homing to DN kidneys, we present a strategy to increase SDF-1 via ultrasound-targeted microbubble destruction. In this study, we developed SDF-1-loaded microbubbles (MB(SDF-1)) via covalent conjugation. The characterization and bioactivity of MB(SDF-1) were assessed in vitro. Target release in the targeted kidneys was triggered with diagnostic ultrasound in combination with MB(SDF-1). The related bioeffects were also elucidated. Early DN was induced in rats with streptozotocin. Green fluorescent protein-labeled MSCs were transplanted intravenously following the target release of SDF-1 in the kidneys of normal and DN rats. The homing efficacy was assessed by detecting the implanted exogenous MSCs at 24 hours. The in vitro results showed an impressive SDF-1 loading efficacy of 79% and a loading content of 15.8 μg/mL. MB(SDF-1) remained bioactive as a chemoattractant. In the in vivo study, SDF-1 was successfully released in the targeted kidneys. The homing efficacy of MSCs to DN kidneys after the target release of SDF-1 was remarkably ameliorated at 24 hours compared with control treatments in normal rats and DN rats. In conclusion, ultrasound-targeted MB(SDF-1) destruction could promote the homing of MSCs to early DN kidneys and provide a novel potential therapeutic approach for DN kidney repair.

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Ultrastructural alterations by transmission electronic microscopy.Notes: After UTMD, the small vessel walls roughened and thinned. Peg-shaped tubers (black arrow in [A]) and pores generated (black arrowhead in [B]), resulting in the discontinuous walls. (C) The normal vessels were intact. (B) The detailed view of the black dashed rectangle of (A).Abbreviation: UTMD, ultrasound-targeted microbubble destruction.
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f5-ijn-9-5639: Ultrastructural alterations by transmission electronic microscopy.Notes: After UTMD, the small vessel walls roughened and thinned. Peg-shaped tubers (black arrow in [A]) and pores generated (black arrowhead in [B]), resulting in the discontinuous walls. (C) The normal vessels were intact. (B) The detailed view of the black dashed rectangle of (A).Abbreviation: UTMD, ultrasound-targeted microbubble destruction.

Mentions: The ultrastructural alterations mainly occurred to the micro-blood vessels after UTMD. Partial vessel walls suffered severe injury, while the contralateral vessels suffered mild injury. Peg-shaped tubers originated from the body of endothelial cells, some of which detached and fell into the vessel lumen. The vessel walls roughened and became thinner than usual (Figure 5A). Part of the vessel walls dissolved to generate several pores, allowing direct communication between the inside vascular lumen and extravascular interstitium through the discontinuous walls (Figure 5B). Large vessels survived with an intact wall structure. In comparison, the vessel wall remained continuous in normal renal tissues (Figure 5C).


Ultrasound-targeted stromal cell-derived factor-1-loaded microbubble destruction promotes mesenchymal stem cell homing to kidneys in diabetic nephropathy rats.

Wu S, Li L, Wang G, Shen W, Xu Y, Liu Z, Zhuo Z, Xia H, Gao Y, Tan K - Int J Nanomedicine (2014)

Ultrastructural alterations by transmission electronic microscopy.Notes: After UTMD, the small vessel walls roughened and thinned. Peg-shaped tubers (black arrow in [A]) and pores generated (black arrowhead in [B]), resulting in the discontinuous walls. (C) The normal vessels were intact. (B) The detailed view of the black dashed rectangle of (A).Abbreviation: UTMD, ultrasound-targeted microbubble destruction.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4263441&req=5

f5-ijn-9-5639: Ultrastructural alterations by transmission electronic microscopy.Notes: After UTMD, the small vessel walls roughened and thinned. Peg-shaped tubers (black arrow in [A]) and pores generated (black arrowhead in [B]), resulting in the discontinuous walls. (C) The normal vessels were intact. (B) The detailed view of the black dashed rectangle of (A).Abbreviation: UTMD, ultrasound-targeted microbubble destruction.
Mentions: The ultrastructural alterations mainly occurred to the micro-blood vessels after UTMD. Partial vessel walls suffered severe injury, while the contralateral vessels suffered mild injury. Peg-shaped tubers originated from the body of endothelial cells, some of which detached and fell into the vessel lumen. The vessel walls roughened and became thinner than usual (Figure 5A). Part of the vessel walls dissolved to generate several pores, allowing direct communication between the inside vascular lumen and extravascular interstitium through the discontinuous walls (Figure 5B). Large vessels survived with an intact wall structure. In comparison, the vessel wall remained continuous in normal renal tissues (Figure 5C).

Bottom Line: The related bioeffects were also elucidated.In the in vivo study, SDF-1 was successfully released in the targeted kidneys.In conclusion, ultrasound-targeted MB(SDF-1) destruction could promote the homing of MSCs to early DN kidneys and provide a novel potential therapeutic approach for DN kidney repair.

View Article: PubMed Central - PubMed

Affiliation: Department of Ultrasound, Third Military Medical University, Chongqing, People's Republic of China.

ABSTRACT
Mesenchymal stem cell (MSC) therapy has been considered a promising strategy to cure diabetic nephropathy (DN). However, insufficient MSCs can settle in injured kidneys, which constitute one of the major barriers to the effective implementation of MSC therapy. Stromal cell-derived factor-1 (SDF-1) plays a vital role in MSC migration and involves activation, mobilization, homing, and retention, which are presumably related to the poor homing in DN therapy. Ultrasound-targeted microbubble destruction has become one of the most promising strategies for the targeted delivery of drugs and genes. To improve MSC homing to DN kidneys, we present a strategy to increase SDF-1 via ultrasound-targeted microbubble destruction. In this study, we developed SDF-1-loaded microbubbles (MB(SDF-1)) via covalent conjugation. The characterization and bioactivity of MB(SDF-1) were assessed in vitro. Target release in the targeted kidneys was triggered with diagnostic ultrasound in combination with MB(SDF-1). The related bioeffects were also elucidated. Early DN was induced in rats with streptozotocin. Green fluorescent protein-labeled MSCs were transplanted intravenously following the target release of SDF-1 in the kidneys of normal and DN rats. The homing efficacy was assessed by detecting the implanted exogenous MSCs at 24 hours. The in vitro results showed an impressive SDF-1 loading efficacy of 79% and a loading content of 15.8 μg/mL. MB(SDF-1) remained bioactive as a chemoattractant. In the in vivo study, SDF-1 was successfully released in the targeted kidneys. The homing efficacy of MSCs to DN kidneys after the target release of SDF-1 was remarkably ameliorated at 24 hours compared with control treatments in normal rats and DN rats. In conclusion, ultrasound-targeted MB(SDF-1) destruction could promote the homing of MSCs to early DN kidneys and provide a novel potential therapeutic approach for DN kidney repair.

Show MeSH
Related in: MedlinePlus